Family gives genetic clue to language

Researchers have taken a large stride toward specifying the first gene known to influence human speech and language capacities.

 They found on chromosome 7 a distinctive stretch of DNA that contains about 100 genes, one of which appears to cause a severe speech and 
language disorder in nearly half the members of an extended English family. The scientists report their finding in the February Nature 
Genetics.

 Prior studies have identified several genes in the same region of chromosome 7 that affect brain development. For now, none of them is a 
leading candidate for the role of language disrupter in the so-called KE family, contend geneticist Simon E. Fisher of the University of 
Oxford in England and his colleagues. Further work will attempt to pin down the culprit, Fisher says.

"Whatever this gene is, it has a significant effect on brain development and is probably involved in the coordination of facial muscle 
movements needed for effective speech," holds study coauthor Faraneh Vargha-Khadem, a psychologist at the Wolfson Centre in London.

 Most disturbances of speech and language occur in one or two members of a family, which greatly complicates the search for underlying genetic 
influences. Of 37 KE family members in four generations, however, 15 display the same severe disruption of the ability to communicate. The 
pattern of inheritance indicates that the disorder results from a single gene inherited from either parent, notes Oxford geneticist Anthony P. 
Monaco, another member of the research team.

 Affected KE family members exhibit a wide range of problems, including difficulties in pronouncing sounds of all kinds, low verbal and 
spatial intelligence, and deficits in grammatical knowledge, Vargha-Khadem asserts. In contrast, other investigators argue that this condition 
centers on a genetically instigated rupture of grammar circuits in the brain.

 Fisher and his coworkers examined the entire genome of 27 KE family members for short chemical sequences that repeat a varying number of 
times from one person to another. A specific chromosome 7 sequence marked a 100-gene region of those suffering from the speech and language 
disorder.

 Intriguingly, the same chromosome 7 segment lies within a larger DNA stretch linked to autism -- a disorder that often includes language 
delays -- in a family study that will appear in the March Human Molecular Genetics. Monaco contributed to that work as well.

 Brain scans show that the affected members of the KE family exhibit disturbed development of several inner-brain structures involved in motor 
control, according to preliminary studies directed by neuroscientist Richard S.J. Frackowiak of the Institute of Neurology in London.

 Unlike the severe, rare condition found in the KE family, the bulk of speech and language disorders probably reflect a number of genetic 
influences, Monaco notes.

"The exciting thing here is that it's now possible to begin picking apart language, one of the highest-order cognitive functions, one gene at 
a time," comments geneticist Dennis Drayna of the National Institute on Deafness and Other Communication Disorders in Rockville, Md.

 The outlook for finding the aberrant gene in the KE family looks promising, Drayna adds, because human genome researchers are rapidly nearing 
the completion of their mapping of chromosome 7.